This is a multidisciplinary research project having a goal of elucidating basic biochemical and pathological mechanisms responsible for arteriosclerotic cardiovascular disease. It is made up of six research projects and three Core laboratories. Project 1 deals with the effect of membrane lipid modification on cell function as well as the regulation of cholesterol and fatty acid biosynthesis in leukocytes. Project 2 deals with the development and regression of atherosclerosis in a primate model. Project 3 deals with the function of human endothelial cells and the interaction between endothelial cells and platelets. Project 4 deals with plasma clotting factors, particularly factor VIII, thrombin, heparin cofactor and the binding of thrombin to cultured endothelial cells. Another aspect of this project deals with the properties of endothelial cells derived from mouse brain blood vessels. Project 5 is a clinical epidemiological project on coronary risk factors in school children. Project 6 concerns the role of lysosomal enzymes in atherosclerosis, with particular attention given to cholesteryl ester hydrolase. These projects are supported by Core laboratories.